Publications

Dernière publication 01/01/2024

Bradykinesia and postural instability in a model of prodromal Synucleinopathy wi

ABSTRACT Alpha-Synuclein (aSyn) accumulation within the extra-nigral neuronal populations in brainstem, including the gigantocellular nuclei...

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    [title] => Bradykinesia and postural instability in a model of prodromal Synucleinopathy wi
    [paragraph] => Bradykinesia and postural instability in a model of prodromal Synucleinopathy withAlpha-Synuclein aggregation in the gigantocellular nuclei
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Authors
Vasileios Theologidis, Sara A. Ferreira, Nanna M. Jensen, Diana Gomes Moreira, Ole A. Ahlgreen, Mads W. Hansen, Emilie D. Rosenberg, Mette Richner, Islam Faress, Hjalte Gram, Poul H. Jensen, Per Borghammer, Jens R. Nyengaard, Marina Romero-Ramos, Christian B. V¦gter, Wilma D. J. van de Berg, Nathalie Van Den Berge, Asad Jan

 Lab

Journal
bioRxiv
Abstract
ABSTRACT
Alpha-Synuclein (aSyn) accumulation within the extra-nigral neuronal populations in brainstem, including the gigantocellular nuclei (GRN/Gi) of reticular formation, is a recognized feature during the prodromal phase of Parkinson disease (PD). Accordingly, there is a burgeoning interest in animal model development for understanding the pathological significance of extra-nigral synucleinopathy, in relation to motor and/or non-motor symptomatology in PD. Here, we report an experimental paradigm for the induction of aSyn aggregation in brainstem, with stereotaxic delivery of pre-formed fibrillar (PFF) aSyn in the pontine GRN of transgenic mice expressing the mutant human Ala53Thr aSyn (M83 line). Our data show that PFF aSyn-induced aggregate pathology in GRN leads to progressive decline in spontaneous locomotion and an early phenotype of postural instability. This early phase of bradykinesia was followed by a moribund stage, characterized by worsening motor performance and impaired survival with substantial aSyn aggregation in several brain regions beyond the GRN. Collectively, our observations suggest an experimental framework for studying the pathological significance of aSyn aggregation in GRN in relation to features of movement disability in PD. With further refinements, we anticipate that this model holds promise as a test-bed for translational research in PD and related disorders.

Keywords/Topics
bradykinesia;postural;instability;model;prodromal;synucleinopathy;synuclein;aggregation;gigantocellular;nuclei
BIOSEB Instruments Used:
Grip strength test (BIO-GS4)
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Une méthode simple pour quantifier objectivement la force musculaire des rats et souris et l'effet de drogues, toxines, maladies musculaires (ex: myopathie) et neurodégénératives. Cette mesure de force est souvent employée en association avec le test de coordination motrice ROTAROD: un sujet présentant une coordination normale montrera des résultats médiocres en cas de faible force musculaire. Un must pour vos recherches sur l'activité, la coordination et le contrôle musculaire: particulièrement utile pour vos études sur les maladies de Parkinson et Huntington.
Nouveautés GS4 - 2023: Écran couleur rétroéclairé (meilleure lisibilité), pédale de remise à zéro, durée de batterie optimisée, taille de mémoire augmentée à 500 valeurs, compteur d'animaux, port USB (transfert de données/charge)

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